Innate Immunity Flashcards
What is innate immunity?
Body’s first line defence against pathogens
Tell me about the physical barriers in the human body
Innate immunity
Everything on the surface (tight junction, eyelids/lashes, epithelial cells, cilia, and mucous membrane)
Tell me about the biological barriers in the body
Innate immunity
Chemical/organismal
Bacteria, saliva, urine, tears, stomach acid, anti-microbial peptides (alpha and beta defensins in bacterial cell membranes)
What is different in the lymphatic system than the cardiovascular system?
Lymphatic vessels carry lymph
Not closed
Where are lymphocytes concentrated?
List lymphatic tissues
Lymph nodes
Lymphatic tissues - spleen, thymus, tonsils, adenoid, appendix, Peyer’s patches
Allows them to intercept microbes before they enter circulation
What is the function of lymph nodes?
Exchange lymphocytes with the lymph
Intercept microbes before they enter circulation
What is the function of appendix lymphoid tissue?
Make antibodies and sensitize T cells (released into lymph)
What is the lymphoid function of the spleen?
- Exchange lymphocytes with blood
- Lymphocytes make antibodies and sensitize T-cells
- Macrophages remove microbes and debris
What is the lymphoid function of the thymus?
- Maturation site for T lymphocytes
- Secretes thymosin
What cells are involved in innate immunity?
- Mononuclear phagocytes (macrophages, dendritic cells)
- Natural killer cells
- Mast cells
- Granulocytes (basophils, eosinophils, and neutrophils)
- Complement proteins
What are characteristic of the innate system cells?
- Highly phagocytic
- Myeloid lineage
- Respond within minutes/hrs of recognizing pathogens
- Short-lived
- Rapid response
- Non-specific
- No memory
What allows lineage tracing of myeloid cells?
Cells differentiate in tissues at different times
What receptors allow innate immune cells to recognize a pathogen?
Pattern Recognition Receptors (PRRs)
4 major types
What are the 4 major types of PRRs?
- Toll-like Receptors (TLRs)
- NOD-like Receptors (NLRs)
- C-type lectin receptors (CLRs)
- RIG-1 like receptors (RLRs)
How do PRRs work?
Recognize Pathogen-Associated Molecular Patterns (PAMPs)
PAMPs - proteins, peptides, carbs, nucleic acids on pathogen surface that the innate immune cells react to
Tell me about TLRs
Toll-like Receptors
- Transmembrane proteins in plasma membrane or endosomes
- On immune and non-immune cells
- Broad range of specificities
- Activates MAP kinase, NFkBm and IRF pathways
Tell me about NLRs
NOD-like Receptors
- Cytoplasmic receptors w many subfamilies
- recognize bacterial, viral, parasitic, and fungal PAMPs
- NOD1 and NOD2 recognize bacterial peptidoglycan
How do NLRs recognize viral and bacterial DNA?
- AIM2 detects viral and bacterial DNA
- Forms signalling complexes called inflammasomes
- Activates caspase-1-mediated processing and IL-1B and IL-18
Tell me about CLRs
C-type lectin receptors
- Transmembrane proteins in plasma membrane
- Recognize glycans on bacteria and fungal walls
- Activates kinase syk and CARD9/MALT1/Bcl-10 adapter complex
Tell me about RLRs
RIG-1 like receptors
- Cytoplasmic receptors of viral DNA
- Signal via mitochondrial adaptor protein MAVS
- Trigger antiviral responses inc type I interferon production
Which PRRs are transmembrane?
CLR - C-type lectin receptors
TLR - Toll-like receptors
What PRRs are cytoplasmic?
NLRs and RLRs
Do cells only have 1 type of PRR?
No, they usually have multiple working at the same time
- There are PRR that are specific for certain PAMPs and DAMPs
What is a consequence of PAMP-PRR interaction?
Interaction leads to downstream signalling –> inflammatory signals and get the innate immune cell ready to communicate with cells of the adaptive immune system
Tell me about DAMPs
Damage-Associted Molecular Proteins
- Inc DNA, mtDNA, ATP, ADP and other components that are normally inside the cell
- PRR will respond to these molecules
- Released when a cell has been dmged
How do innate immune cells get rid of pathogens?
Give steps
Phagocytosis
- Starts PRR and PAMP interact (opsinization)
- actin rearrangement of immune cell to surround pathogen —> phagosome
- Lysosomes fuse phagosome —> digestion
- Immune cells can also present the phagosome to the adaptive immune system cells via MHC
What are opsonins?
Proteins that bind to foreign bodies to make it easier for phagocytes to stick to the pathogen
Phagocytes have receptors that bind to opsonins
What are the main phagocytic cells?
- Macrophages
- Neutrophils
- Dendritic cells
What is the most resilient phagocyte?
Macrophage
What are the cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
Mediated by increase vascular diameter
What is inflammation?
Altered blood flow, increased immune cells, foreign antigen removal, and healing of dmged tissue
- Response consisting of vasodilation (arteriole and caps)
- Increase cap permeability from histamine
- Edema
Do pathogens always cause disease?
No; most people with a healthy immune system do not get a disease from encountering a pathogen
What is the function of coughing/sneezing?
Helps expel foreign particles from the respiratory tract
What causes immune cells to move to a site of infection or injury?
Chemotactic signals
What cells are the bridge between the innate and adaptive immune system?
- γ δ T-cells
- natural killer T cells
Do immune cells only respond to infection?
No, they will also respond to injury by recognizing DAMPs
These cells have different names depending on the tissue they’re residing. Their function stays the same in all tissues
Macrophages
Does the speed of the innate immune response get faster with subsequent exposure to the same antigen?
No, takes the same time regardless of previous exposure
What is opsonization?
Flagging of foreign bodies to make phagocytosis easier for phagocytic cells
- PRRs on phagocytic cells recognize opsonins and engulf the antigen
How do immune cells migrate from the blood vessel into tissue?
- Endothelial activation local cells release inflammatory signals —> increased adhesion molecules (selectin)
- Rolling immune cells stick and roll along vessel lumen
- Activation chemokines bind to immune cell —> integrin activation on cell —> affinity for endothelial adhesion molecules
- Firm adhesion intergrins bind —> rolling stops and cell anchors to vessel wall
- Migration squeezes through tight junctions via actin rearrangement then moves to where chemokines are strongest
